In living hepatic parenchymal cells are enzyme systems responsible for the metabolism of compounds foreign to the organism. The enzymatic reactions are catalyzed by mixed function oxidases (monooxygenases) located in the endoplasmic reticulum, and require both molecular oxygen and NADPH. NADH can stimulate the NADPH supported drug hydroxylation reactions (NADH synergism). The proposed research will investigate the precise role of mitochondria in affecting drug biotransformation reactions. The rate of electron flow to and drug oxidation by the endoplasmic reticulum monooxygenase in the presence and absence of Krebs cycle substrates will be determined. Assessment of the role of cytochrome b5 in drug metabolism is necessary in order to determine whether the hemoprotein may be the bridge or link between the two organelles. This is an important consideration since both organelles contain the NADH cytochrome c reductase system whose components are the flavoprotein, NADH cytochrome b5 reductase and the hemoprotein, cytochrome b5.